EP0720599A1 — Hydroxy-substituted azetidinone compounds useful as hypocholesterolemic agents

USPTO Abstract

Hydroxy-substituted azetidinone hypocholesterolemic agents of formula (Ia) or a pharmaceutically acceptable salt thereof, wherein: Ar?1 and Ar2¿ are aryl or R4-substituted aryl; Ar3 is aryl or R5-substituted aryl; X, Y and Z are -CH¿2?-, -CH(lower alkyl)- or -C(dilower alkyl)-; R and R?2¿ are -OR6, -O(CO)R6, -O(CO)OR9 or -O(CO)NR?6R7; R1 and R3¿ are H or lower alkyl; q is 0 or 1; r is 0 or 1; m, n and p are 0-4; provided that at least one of q and r is 1, and the sum of m, n, p, q and r is 1-6; and provided that when p is 0 and r is 1, the sum of m, q and n is 1-5; R4 is selected from lower alkyl, R5, -CF3, -CN, -NO2 and halogen; R5 is selected from -OR6, -O(CO)R6, -O(CO)OR9, -O(CH¿2?)1-5OR?6¿,-O(CO)NR?6R7, -NR6R7, -NR6(CO)R7, -NR6(CO)OR9, -NR6(CO)NR7R8, -NR6SO¿2R?9, -COOR6, -CONR6R7, -COR6, -SO¿2NR6R7, S(O)¿0-2R?9, -O(CH¿2?)1-10-COOR?6¿, -O(CH¿2?)1-10CONR?6R7¿, -(lower alkylene)COOR6 and -CH=CH-COOR?6; R6, R7 and R8¿ are H, lower alkyl, aryl, or aryl-substituted lower alkyl; R9 is lower alkyl, aryl or aryl-substituted lower alkyl; are disclosed, as well as a method of lowering serum cholesterol by administering said compounds, alone or in combination with a cholesterol biosynthesis inhibitor, pharmaceutical compositions containing them, and a process for preparing them.